1. Field of the Invention
The invention relates to low solubility drug-coated bead compositions, capsules filled therewith and method of preparation thereof, especially wherein the low solubility drug is an antiandrogenic steroid and most especially wherein the antiandrogenic steroid is (5.alpha.,17.alpha.)-1'-(methylsulfonyl)-1'H-pregn-20-yno[3,2-c]pyrazol-17 -ol.
2. Information Disclosure Statement
Harrison et al. U.S. Pat. No. 4,717,569 issued Jan. 5, 1988 describes pharmaceutical compositions
. . . for oral administration of a polycyclic medicament having a solubility in water and aqueous media at ambient temperatures of less than 1 part of the medicament in from 5,000 to greater than 10,000 parts by weight of the medium which comprises a plurality of beads, each bead comprising particles of finely divided solid medicament bound together by a binder soluble in water and aqueous media at all pH values normally found in the gastrointestinal tract, and preferably a pharmacologically acceptable wetting agent, said plurality of beads together constituting a unit dose. In a preferred embodiment, the unit dosage form is enclosed in a gastric juice-soluble material, such as gelatin. PA1 for oral . . . administration . . . in solid dosage form including capsules, tablets . . . Conventional pharmaceutically acceptable vehicles and techniques are used in preparing these dosage forms.
The beads can be "sugar/starch bead[s]". The compositions are described as having been prepared by coating the beads with an aqueous suspension of the medicament and binder and optional wetting agent and then encapsulated. Five examples are described wherein the medicament is "17a-pregna-2,4-diene-20-yno[2,3-d]isoxazol-17-ol( . . . Compound A)" and the binder is hydroxypropylmethylcellulose, one in which no wetting agent is included, four in which sodium lauryl sulphate is included as wetting agent, and three in which polyvinylpyrrolidone is included as a second binding agent. Improved human bioavailablity of the medicament is shown by favorable comparison of several described formulations with corresponding conventional starch-lactose-talc-magnesium stearate dry powder capsule formulations.
Christiansen et al. U.S. Pat. No. 4,684,636 issued Aug. 4, 1987 describes antiandrogenic sulfonylsteroidopyrazoles including (5.alpha.,17.alpha.)-1'-(methylsulfonyl)-1'H-pregn-20-yno[3,2-c]pyrazol-17 -ol as the product of EXAMPLE 1 and pharmaceutical compositions thereof in general including those
The patent does not describe any such composition specifically.